Terminal Villi Research Articles

Immunocytochemical Localization of Endothelin-1 in Human Placenta from Normal and Preeclamptic Pregnancies

Objective. The aim of this study was to examine the distribution of endothelin-1 (ET-1) in the human placenta at different gestational ages and to determine whether differences in ET-1 immunoreactivity occurred in preeclamptic compared with uncomplicated pregnancies.Methods. Localization of ET-1 was investigated by the immunoperoxidase technique in first-trimester, second-trimester, and term human placentas from normal pregnancies and in placentas from preeclamptic pregnancies.Results. In normal placentas from all gestational ages studied, endothelin-1 immunoreactivity (ET-1 IR) was specifically detected in the endothelium of the fetal vessels and in the syncytiotrophoblast. ET-1 IR was also expressed by the villous cytotrophoblast of first- and second-trimester normal placentas. The extravillous cytotrophoblast of the basal and chorionic plates also exhibited ET-1 IR, but with varying degrees of intensity. In preeclamptic placentas, the expression of ET-1 IR was uneven with a negative staining in all placentas from pregnancies between the 29th and 32nd weeks of gestation. The expression of ET-1 IR was most intense in some syncytiotrophoblast tissue in the terminal villi after the 33rd week of gestation. In placentas from preeclamptic pregnancies between the 35th and the 36th weeks of gestation, strong ET-1 IR expression was evident in the endothelium of fetal vessels and in the syncytiotrophoblast. Regardless of gestational age, ET-1 IR was also observed in the extravillous cytotrophoblast of the basal and chorionic plates of preeclamptic placentas.Conclusion. This study demonstrates that ET-1 IR is widely distributed in the human placenta and provides further evidence to support the concept that ET-1 plays an important role as a modulator of vascular tone in the uteroplacental and fetoplacental units and may participate in the pathogenesis of preeclampsia.

Placental vascular morphogenesis

Appropriate growth and development of the placenta is essential for fetal growth and wellbeing, and indeed may be an important factor in determining adult health.1 As the fetus grows its demands increase and the capacity of the placenta to facilitate transfer between the fetal and maternal circulations increases as gestation progresses. The principal units for diffusional exchange of oxygen are the terminal villi, and these develop in the third trimester. It is thought that capillary growth within the villi drives the growth of these structures which are characterized by a high proportion of their volume being occupied by fetal capillaries and extreme thinning of the trophoblast and endothelial cell layers. In the first trimester the P O2in the intervillous space is low and rises sharply at the start of the second. Endothelial growth is influenced by a variety of soluble factors, and several of these are regulated by oxygen, for example, vascular endothelial growth factor (VEGF), angiopoietin 2, and soluble flt (a VEGF antagonist). Thus, fetal demand may regulate villous growth and differentiation by altering local P O2which, in turn, modulates growth factors (or their antagonists) to regulate endothelial growth and vessel re-modelling.

Development of the placental villous tree and its consequences for fetal growth

Co-ordinated development of the fetal villous tree of the placenta is necessary for continued fetal growth and well-being. Before fetal viability, blood vessel development within the developing immature intermediate villi (IIV) is characterized by branching angiogenesis, such that the placenta expands to produce 10–16 generations of stem villi. Once fetal viability is attained, a developmental switch occurs to form large numbers of gas-exchanging terminal villi (TV) by non-branching angiogenesis in mature intermediate villi (MIV). Several growth factors, including vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), angiopoietins, and angiostatins are produced within the villi and act locally, via their receptors, to control angiogenesis. Their relative contributions to placental vascular development are not fully understood at the present time. Severe early-onset intrauterine growth restriction (IUGR) is characterized by absent/reversed end-diastolic flow velocity (ARED) in the umbilical arteries, leading to fetal hypoxia, acidosis and a substantial rise in perinatal mortality and morbidity. The placentas from such cases show a deficit in peripheral villous development, which may be perpetuated by the effects of oxygen (delivered by maternal blood into the intervillous space) upon VEGF-directed angiogenesis, the so-called ‘placental hyperoxia’ theory of villous maldevelopment. Trophoblast apoptosis is a significant feature of early-onset IUGR and may explain poor flow-independent transfer of nutrients to the fetus. Finally, since transgenic mouse studies highlight the importance of trophoblast-derived transcription factors for placental villous (labyrinth) development, it is possible that the villous trophoblast controls the orderly development of the underlying mesoderm and blood vessels into the fetal villi.

Villous sprouting: fundamental mechanisms of human placental development.

There is increasing evidence that maldevelopment of the placental villous tree can play an important role in the pathogenesis of various pregnancy diseases. In this review we present the most recent advances of cellular and molecular mechanisms involved in the early formation of chorionic villi. In particular we focus our attention on the structural events during early villous sprouting leading to the formation of the mesenchymal villi which are the forerunners of all other villous types, i.e. immature intermediate villi, stem villi, mature intermediate villi and terminal villi. Early villous sprouting starts as 'hot spots' which are circumscribed areas consisting of highly proliferating cytotrophoblastic and stromal cells. The post-proliferative cytotrophoblastic cells fuse with the overlying syncytium leading to the formation of the trophoblastic sprouts. When villous mesenchyme invades the trophoblastic sprouts, the latter are transformed into villous sprouts. The vascularization of the villous sprouts leads to the formation of the mesenchymal villi, the most basic villous type. This process is repeated throughout pregnancy. We analyse the influence of various extracellular matrix molecules, e.g. tenascin and hyaluronic acid, on the formation of hot spots and mesenchymal villi as well as the transformation of the latter in other villous types. We present a critical survey on the data on vessel formation related to villous sprouting and morphogenesis of mesenchymal villi as well as the expression of various angiogenic factors and their receptors.

Molecular Organization of Tight and Adherens Junctions in the Human Placental Vascular Tree

Tight and adherens junctions are major determinants of endothelial integrity. Molecules present therein have been implicated in vascular permeability, stability of junctions, angiogenesis and intracellular signalling. Using immunofluorescence and confocal scanning microscopy, the adherens junctions (AJs) in human placental vessels were found to contain the entire cadherin–catenin complex predicted from in vitro studies. Vascular endothelial cadherin (VE-cadherin) clusters were co-localized with β-catenin, an important signal transduction ligand, and with α-catenin, which is thought to link the complex to the peri-junctional actin. Antibodies to plakoglobin, a molecule shown to be a component of stable adherens junctions, revealed immunoreactivity in clefts of stromal villous vessels, but weak or negative immunoreactivity in intermediate and terminal villi. Tight junctional molecules demonstrated a differential surface expression. Within the same villous tree, arteries, veins and arterioles contained occludin but the exchange vessels in terminal villi were immunonegative. ZO-1, however, was present throughout. Ultrastructurally, there were no differences in frequency, position or dimension of tight junctions in these vessels. They showed a consistent 4nm separation between outer membrane leaflets regardless of their location in the vascular tree. Occludin is not necessary for formation of tight junctions in the placenta; it may have an accessory role providing stability or added adhesiveness to tight junctions of large vessels. Its absence in terminal villous microvessels, along with the weak plakoglobin immunoreactivity in AJs, suggest that the junctions here are less stable. This may allow the increased plasticity necessary in terminal villi for continual growth, proliferation and solute exchange.

Quantitative computer image analysis of chondroitin sulfate A expression in placentas infected with Plasmodium falciparum.

Most pathological conditions resulting from infection with the human malaria parasite Plasmodium falciparum occur as a consequence of the sequestration by several adhesion molecules of parasite-infected red blood cells (IRBCs). Recent reports have provided evidence that placental vascular endothelial ligands for IRBCs were mostly restricted to chondroitin sulfate A (CSA). The expression of CSA in malaria-infected placentas was investigated in a prospective case-control study in a hypoendemic area (Dakar, Senegal). The tissue distribution of CSA was measured in the terminal villi by immunostaining combined with image processing in 20 infected and 20 noninfected frozen sections of placenta. The villous surface immunostained by anti-CSA antibody was higher in infected than in noninfected placentas (p<0.03), in placentas with active infection than in those with past chronic infection (p<0.05), and in infected placentas with positive imprints than in those with negative imprints (not significant; p=0.06). Labeling was found in the extracellular matrix and in endothelial and stromal cells of all the placentas. Syncytiotrophoblast immunostaining was detected in all placentas associated with active or active chronic infection (n=7) but in only 4/13 placentas with past chronic infection (p<0.01). The presence of P. falciparum in the imprint was significantly correlated with immunostaining of CSA in syncytiotrophoblasts (p=0.003). These results suggest that CSA can play an important role in the sequestration of P. falciparum in human placentas during the acute phase of infection.

Ontogeny of Hepatocyte Growth Factor (HGF) and Its Receptor (c- met) in Human Placenta : Reduced HGF Expression in Intrauterine Growth Restriction

Severe intrauterine growth restriction (IUGR) is characterized by abnormal placentation. Mouse gene knockout studies show that an absence of either hepatocyte growth factor (HGF) or its receptor, c-met, leads to intrauterine death secondary to severe IUGR with deficient placentation. In this study, immunocytochemistry localized HGF protein throughout placental villi across gestation, whereas c-met protein was localized only to the perivillous trophoblast and vascular endothelium. Within the IUGR placentae, a reduction in HGF immunostaining within the villous stroma was observed. HGF mRNA was strongly expressed in the perivascular tissue around the stem villous arteries throughout gestation, with weaker expression within the villous stroma and the terminal villi. c-met mRNA expression was limited to the perivillous trophoblast, particularly in the first trimester, with only a faint hybridization signal from the villous stroma. Placental mRNA expression was examined quantitatively using a ribonuclease protection assay: HGF and c-met mRNA expression increased from the first to the second trimester, reaching a zenith before decreasing again through the third trimester to term. HGF mRNA levels were significantly reduced in the IUGR placentae (P = 0.036), whereas c-met mRNA expression was within the normal range for gestation. These findings suggest that HGF derived from the perivascular tissue of stem villous arteries may play an important role in controlling normal villous development. Whereas reduced expression of HGF within IUGR placentae does not prove a causative link with abnormal villous development, the association lends support to this possibility.

Placental pathology of absent and reversed end-diastolic flow in growth-restricted fetuses

Objective To identify placental histopathology associated with absent and reversed end-diastolic flow demonstrated by umbilical artery (UA) Doppler velocimetry in fetal growth restriction (FGR). Methods Between January 1989 and June 1995, 64 consecutive, nonanomalous singletons at less than the tenth percentile for birth weight were admitted to the neonatal intensive care unit, with UA Doppler velocimetry obtained within 3 days of delivery; 54 of the 64 (84%) had placental histopathology. Umbilical artery Doppler wave forms were classified as having end-diastolic flow ( n = 26), and either absent ( n = 20) or reversed end-diastolic flow ( n = 8). Blinded review of placental histology scored lesions in categories of intraplacental vaso-occlusion, uteroplacental vascular pathology, chronic inflammation, and coagulation. Results Using cases of FGR with end-diastolic flow present as the control population, we found that absent end-diastolic flow cases had significantly more fetal stem vessels with medial hyperplasia and luminal obliteration, and cases of reversed end-diastolic flow had significantly more poorly vascularized terminal villi, villous stromal hemorrhage, “hemorrhagic endovasculitis,” and abnormally thin-walled fetal stem vessels (each P Conclusion In FGR, UA Doppler velocity wave forms do not demonstrate a continuum of placental lesions in which reversed end-diastolic flow reflects more severe placental histopathology than absent end-diastolic flow and enddiastolic flow present. As expected, absent end-diastolic flow cases had more occlusive lesions of the intraplacental vasculature. In reversed end-diastolic flow, lesions suggesting vascular remodeling and/or damage by pathologic conditions of intraplacental flow predominated.

Doppler flow velocity waveforms of the umbilical arteries correlate with intravillous blood volume

OBJECTIVE: My purpose was to measure the volume of the fetoplacental vessel tree and to relate findings to Doppler flow patterns of the umbilical arteries. STUDY DESIGN: One hundred sixty placentas were examined by means of standardized random block placental histomorphometry after delivery and the results were compared with antenatal Doppler findings. RESULTS: There was a high correlation ( r = –0.703) between the intravillous blood volume obtained from measurements of intermediate and terminal villi and the Doppler flow velocity waveforms detected within the last week before delivery. Moreover, the reduced size of a vessel tree less than 85 mL is highly predictive of perinatal complications, such as fetal growth restriction, low umbilical artery pH values after birth, reduced Apgar scores, and cesarean section for fetal distress. CONCLUSION: These data suggest that reduced end-diastolic flow velocities in the umbilical arteries are associated with elevated fetoplacental impedance owing to reduced vascularization of intermediate and terminal villi. (Am J Obstet Gynecol 1998;179:540-3.)

BCL-2 expression in the human placenta and its correlation with fibrin deposits.

The human placenta performs numerous functions during its limited lifespan and its survival is a necessary prerequisite for fetal nutrition, even in unfavourable conditions. BCL-2 is a proto-oncogene implicated in the regulation of cell death and survival without affecting cell proliferation. An extracellular matrix molecule involved in the reparative and degenerative processes in the human placenta is fibrin. We have analysed by immunohistochemistry the expression of BCL-2 and correlated it with fibrin deposits in placental tissues. In first and third trimester placentas BCL-2 was expressed in the syncytiotrophoblast. Only a few mesenchymal villi (first trimester) or terminal villi (third trimester) showed no staining in the syncytiotrophoblast. Villous cytotrophoblast, mesenchymal cells of the villous cores and extravillous cytotrophoblast of cell columns and cell islands were all negative for BCL-2. BCL-2 expression was enhanced in the syncytiotrophoblast overlying subtrophoblastic fibrin deposits. However, discontinuities and/or variations in intensity of BCL-2 expression characterized not only the villi showing perivillous fibrinoid but also those villi with a massive presence of fibrinoid in their cores. These data suggest that BCL-2 may be necessary for the preservation of the placenta during gestation as well as for the reparative processes of the trophoblast.

A morphometric study of maternal smoking on apoptosis in the syncytiotrophoblast

Objectives: To study syncytiotrophoblast apoptosis in the placenta of smoking and non-smoking pregnant women. Methods: Twelve neonates, pregnancies and placentas were available for study. Eight mothers smoked during pregnancy and the remaining four were non-smokers used as control subjects. The main outcome measure was the apoptotic syncytiotrophoblast index for each group. Apoptosis was detected by immunohistochemistry using the TUNEL method and quantitatively measured using a Merz grid. The apoptotic syncytiotrophoblast index was calculated as the ratio of mean apoptotic labeling to percent terminal villus area using high-power field microscopy. Results: Significant differences in apoptotic syncytiotrophoblast index were observed between the control group (15.06 ± 3.72) and the smoker group (1.66 ± 1.74) ( P < 0.0001, Mann-Whitney test), but no differences were detected in clinical or morphometric data between groups. Conclusions: The human placental syncytiotrophoblast undergoes apoptosis and this process is associated with inhibition of apoptosis by the smoking habit. The same way as the presence of trophoblast apoptosis is associated with modifications of the maternal-fetal exchange, the inhibitory effect of the smoking habit on syncytiotrophoblast could be responsible for the poor prognosis of pregnancy in the presence of maternal smoking.

Fetal villosity and microvasculature of the bovine placentome in the second half of gestation.

The architecture of the fetal villous tree and its vasculature in the bovine placentome were studied in the second half of gestation using both conventional histology and histology of ink-filled blood vessels. These were compared with corrosion casts of plastic fillings of the vasculature, prepared for scanning electron microscopy. This combination of morphological methods allows perception of the villous tree throughout gestation from broad-conical to tall-conical form where branch ramification occurs mainly at right angles to the stem. The stem villus typically contains a single central artery and several peripheral veins arranged in parallel. The proximal branches to the stem, the intermediate villi, contain a central arteriole and accompanying venules. The distal branches, the terminal villi, enclose capillary convolutions which consist of an afferent arterial capillary limb, capillary loops and efferent venous capillary limbs. Vascular interconnections exist within the terminal villi, as capillaries or venules between the capillary convolutions, serially bridging them in up to 5 places, and as capillary anastomoses between the capillary loops. Coiling and sinusoidal dilatations of these loops develop near the end of gestation. The intraplacentomal rearrangement of villous trees with progressive gestation and their morphological vascular adaptations are discussed in relation to placental function, including the ever increasing need for transplacental substance exchange. This adaptation allows the blood to traverse the shortest possible arterioarteriolar route to the periphery of the trees where exchange takes place. The need for an increasing blood flow stimulates capillary growth and at the same time optimises the blood flow reaching the placental barrier represented by the vessel cast surface. The capillaries also carry the blood back into the very voluminous system of venules and veins where back diffusion may occur. The total volume of terminal villi of bovine placentome, the 'working part' of villous trees, hence distinctly increases with respect to the stem and intermediate villi, the 'supplying part' of the villous tree. In morphological terms the efficiency of the bovine transplacental diffusional exchange is higher than in the closely related 'co-ruminants' sheep and goats and distinctly higher when compared with the human placenta.

Immunohistochemical Distribution of Vascular Endothelial Growth Factor in the Human Placenta Associated with Hydrops Fetalis

The purpose of this study was to determine the distribution and the expression of vascular endothelial growth factor (VEGF) in human placentas obtained from 22 cases of nonimmunologic hydrops fetalis (NIHF), ranging from 25 to 41 weeks of gestation, as compared with those in 75 normal placentas. The terminal villi were examined immunohistochemically using rabbit anti-human VEGF immunoglobulin G. The expression of VEGF in the terminal villi was assessed by the ratio of the VEGF-positive area to the capillary area. Among the 22 placentas, 18 placentas were hydropic and appeared to be histologically immature, and the other 4 placentas, whose fetuses eventually recovered before their deliveries, were nonhydropic. In both the HF and normal placentas, syncytiotrophoblasts expressed VEGF in the villi throughout gestation. VEGF was also expressed by stromal cells in the terminal villi of normal placentas in only the first trimester, whereas its expression continued until the term of pregnancy in 12 of 18 HF placentas. The ratio of the VEGF-positive area to the capillary area was significantly higher in the terminal villi of all hydropic HF placentas than in those of the normal placentas but was entirely the same in the four nonhydropic placentas as in the normal control placentas. These results suggest that the persistent expression of VEGF by stromal cells in the hydropic villi of NIHF, in addition to the VEGF expression by syncytioptrophoblasts, seems to be a reaction to poor villous vascular development and to participate in the regulatory mechanisms of vascular function including angiogenesis and permeability.

High altitude and spontaneous preterm birth

Objective: To study the association between high altitude and spontaneous preterm birth. Methods: Eleven placentas from cases of high altitude (3000 m) spontaneous preterm deliveries with no clinical predisposing cause were collected in Abha, a city of southern Saudi Arabia. The placentas were examined histologically using sections stained by periodic acid-Schiff and hematoxylin-eosin. The mean percentages of villi with syncytial knots and cytotrophoblastic cells were determined. Results: Histology of the placenta samples showed an excessive formation of syncytial knots (45.4 ±13.3%) and cytotrophoblastic cells (52.7 ±15.2%) at terminal villi. Conclusion: The enhanced formation of syncytial knots and cytotrophoblastic cells is a histological feature of placental hypoxia, which may be secondary to maternal hypoxia resulting from high altitude hypoxia. Since placental hypoxia is associated with an increased incidence of spontaneous preterm birth, we suggest that high altitude may be involved in the etiology of spontaneous preterm birth.

Structural analysis of placental terminal villi from growth-restricted pregnancies with abnormal umbilical artery doppler waveforms

The abnormal umbilical artery Doppler waveform represented by absent end-diastolic flow velocity (AEDFV) identifies a group of preterm small-for-gestational age fetuses that are at high risk of perinatal death due to chronic fetal hypoxia. The placental ischaemia that results from inadequate trophoblast invasion of spiral arterioles leads to an assumption of placental villous hypoxia, though an alternative explanation is that the placenta fails to adequately transfer oxygen to the fetus from the intervillous space. Because oxygen transport takes place within the terminal villi, we undertook the first detailed studies of villous ultrastructure structure and immunohistochemistry in order to determine the likely origin of fetal hypoxia in this condition. Terminal villi were examined ultrastructurally using transmission electron microscopy and by immunohistochemical localization of matrix molecules (laminin and collagens I, III and IV) and a marker of cell proliferation (MIB-1), in 16 small-for-gestational age pregnancies with AEDFV in the umbilical artery [deemed to have intrauterine growth restriction (IUGR)] and in 16 gestation age-matched controls. Terminal villi from the IUGR cases were smaller in diameter (P < 0.02) and had several abnormal features in comparison with the controls; increased syncytial nuclei (P < 0.01), reduced cytotrophoblast nuclei (P < 0.01), thickened basal lamina (P < 0.01), and increased stromal deposition of collagens and laminin. The amount of proliferating cytotrophoblast was reduced in the IUGR group (P < 0.014) and the degree of capillary erythrocyte congestion within terminal villous capillaries was increased (P < 0.001). Several of the structural differences in the terminal villi of the IUGR group such as reduced cytotrophoblast proliferation and stromal fibrosis are incompatible with the prevailing view of placental hypoxia in IUGR. Rather thickening of the basal lamina and congestion of the capillaries by erythrocytes are predicted to limit oxygen transfer from the intervillous space to the fetus and may represent an equilibration of oxygen tension between intervillous space and the terminal villi. Despite the known reduction in uteroplacental blood flow in IUGR, fetoplacental blood flow is compromised to a far greater extent in the presence of AEDFV such that maternal blood leaving the placenta has a higher oxygen content than under normal circumstances.

Expression of cell adhesion molecules in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth retardation

Platelets and neutrophils are involved in maternal placental vascular damage in pre-eclampsia. Recruitment of these cells is probably mediated by cell adhesion molecules expressed at the uteroplacental bed. It remains controversial as to whether platelets and neutrophils mediate damage to trophoblast or villous vasculature. The purpose of this study was to determine the expression of cell adhesion molecules in placentae from normal pregnancies and pregnancies complicated by pre-eclampsia and intrauterine growth retardation (IUGR). Immunostaining for platelet endothelial cell adhesion molecule (PECAM) and intercellular adhesion molecule-1 (ICAM-1) was localized mainly to the endothelium of stem villi, intermediate villi, terminal villi and decidual vessels. Scattered staining for ICAM-1 was also evident in the stroma and fetal membranes. The endothelium of stem villi, intermediate villi and terminal villi were all negative for vascular cell adhesion molecule-1 (VCAM-1) and E-Selectin. PECAM, ICAM-1 and ICAM-2 mRNA were all detectable in normal placentae using northern blotting analysis whereas mRNA for E-Selectin and VCAM-I were both undetectable. There were no differences in cell adhesion molecule immunostaining or mRNA expression in placentae from pregnancies complicated by pre-eclampsia and IUGR inconclusion, expression of cell adhesion molecules in placentae from pre-eclampsia and IUGR are consistent with a normal physiological role in vascular function.

Correlation between umbilical arterial flow and placental morphology.

Umbilical artery blood velocity waveforms were compared with the morphological aspects of the vascular bed of 30 placentas using quantitative methods. An abnormal pulsatility index was found to be highly correlated with a lower number of arteries in the tertiary stem villi as well as a lower placental weight and birth weight. The reduction in the number of arteries seems to be due to an early developmental arrest of placental angiogenesis and is partly compensated for by increased formation of capillaries in the terminal villi, since the number of capillaries is independent of the number of arteries.

Immunohistochemical characterization of placental nitric oxide synthase expression in preeclampsia

OBJECTIVE: Our purpose was to compare the expression of endothelial nitric oxide synthase in the placenta and umbilical cord of preeclamptic placenta with that of the normotensive placenta. STUDY DESIGN: We compared placental endothelial nitric oxide synthase expression in preeclamptic ( n = 3) with that in normal ( n = 3) pregnancies. Frozen sections of umbilical cords, chorionic plate vessels, and terminal villi were immunostained with a monoclonal endothelial nitric oxide synthase antibody (H32). RESULTS: No difference in endothelial nitric oxide synthase immunostaining in the endothelium of the umbilical cord artery and vein, chorionic plate vessels, and stem villous vessels was found between preeclamptic and normotensive pregnancies. In contrast, in the preeclamptic placentas endothelial nitric oxide synthase immunostaining was seen in the small terminal villous vessels with underlying smooth muscle layer. In the syncytiotrophoblast endothelial nitric oxide synthase immunostaining appeared primarily apical in location and diffuse in distribution in the preeclamptic placentas but primarily basal and punctate in the normotensive placentas. CONCLUSIONS: Differences in endothelial nitric oxide synthase expression in terminal villous vessels and in syncytiotrophoblast may be a result of vascular alterations or damage that take place in the placenta in preeclampsia. These differences may alter the regulation of blood flow in the fetal and maternal placental vasculatures in preeclampsia.

Placental histomorphometry and morphometric diffusing capacity of the villous membrane in pregnancies complicated by maternal iron-deficiency anemia

OBJECTIVE: our purpose was to determine the morphometric diffusing capacity of the human placental villous membrane in cases of maternal iron-deficiency anemia. STUDY DESIGN: Material from 10 term placentas from mothers with hemoglobin levels < 10 gm/100 cm 3 was compared stereologically with control material from women with normal hemoglobin concentrations matched for age and parity. Data were compared with Student t test. RESULTS: Birth and placental weights were constant between the two groups. Maternal anemia was associated with a significant reduction in both volume and surface area of intermediate and terminal villi (157.8 vs 234.5 cm 3 and 9.5 vs 14.9 m 2, respectively). There was a concomitant rise in the volume of pathologic areas (32.1 vs 4.1 cm 3). Harmonic mean thickness of the villous membrane was significantly less in the anemia cases (5.86 vs 7.15 μm), because of an increase in volume fraction of the fetal capillaries. Consequently, the morphometric diffusing capacity of the villous membrane was maintained (4.49 vs 5.31 cm 3 · min −1 · mm Hg −1, t = 1.04, p > 0.05). CONCLUSIONS: There is a reduction rather than an enlargement of the placental villous tree in cases of maternal anemia. This may be because of underlying malnutrition. Nonetheless, the placenta adapts through thinning of the villous membrane so that diffusing capacity is maintained at normal levels.

Structural analysis of placental terminal villi in pregnancies complicated by absent end-diastolic blood flow velocity in the umbilical artery

Structural analysis of placental terminal villi in pregnancies complicated by absent end-diastolic blood flow velocity in the umbilical artery